自噬通过调节小鼠肾脏AQP2表达和肾素-血管紧张素系统对尿液浓缩能力的差异调节。

IF 3.7 2区 医学 Q1 PHYSIOLOGY American Journal of Physiology-renal Physiology Pub Date : 2023-10-01 Epub Date: 2023-08-17 DOI:10.1152/ajprenal.00018.2023
Chuanming Xu, Xiaoli Yi, Le Tang, Hui Wang, Shuhan Chu, Jun Yu
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引用次数: 1

摘要

自噬是一种“自我吞噬”的细胞过程,在肾脏病理生理学中发挥着重要作用。然而,在生理条件下,自噬对尿液浓缩能力的影响仍然未知。本研究旨在确定自噬在抗利尿过程中维持尿液浓缩能力的相关性和机制。小鼠肾皮质和髓质对缺水(WD)的自噬反应程度不同。肾皮质中的自噬活性水平最初受到WD的抑制,然后以时间依赖的方式受到WD的刺激。在48小时WD期间,雷帕霉素(Rapa)而不是3-甲基腺嘌呤(3-MA)损害了小鼠的尿液浓缩能力,同时抑制了肾水通道蛋白2(AQP2)、V2受体(V2R)、肾素和血管紧张素转换酶(ACE)的表达,以及血浆和尿液中的前肾素/肾素、血管紧张素II(ANG II)和醛固酮水平。相反,3-MA和氯喹(CQ)抑制了WD72小鼠的尿液浓缩能力,同时下调了肾皮质AQP2和V2R的表达。3-MA和CQ进一步增加了WD72小鼠肾髓质中AQP2和V2R的表达。与3-MA和CQ相比,Rapa给药在WD72小鼠的上述参数上产生了完全相反的结果。此外,3-MA和CQ消除了WD72小鼠血浆和尿液中前肾素/肾素、ANG II和醛固酮水平的上调。总之,我们的研究表明,自噬通过对WD.NEW和NOTEWORTHY过程中肾脏AQP2/V2R和ACE/ANG II信号的差异调节来调节尿液浓缩能力。自噬对细胞存活具有双重作用,在肾脏病理生理学中起着重要作用。我们首次报道了一种新的自噬功能,它在生理条件下控制尿液浓缩能力。我们发现,缺水(WD)以时间依赖的方式不同地调节小鼠肾脏中的自噬,自噬主要通过调节WD小鼠肾皮质中的AQP2/V2R和ACE/ANGII信号来调节尿液浓缩能力。
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Differential regulation of autophagy on urine-concentrating capability through modulating the renal AQP2 expression and renin-angiotensin system in mice.

Autophagy, a cellular process of "self-eating," plays an essential role in renal pathophysiology. However, the effect of autophagy on urine-concentrating ability in physiological conditions is still unknown. This study aimed to determine the relevance and mechanisms of autophagy for maintaining urine-concentrating capability during antidiuresis. The extent of the autophagic response to water deprivation (WD) was different between the renal cortex and medulla in mice. Autophagy activity levels in the renal cortex were initially suppressed and then stimulated by WD in a time-dependent manner. During 48 h WD, the urine-concentrating capability of mice was impaired by rapamycin (Rapa) but not by 3-methyladenine (3-MA), accompanied by suppressed renal aquaporin 2 (AQP2), V2 receptor (V2R), renin, and angiotensin-converting enzyme (ACE) expression, and levels of prorenin/renin, angiotensin II (ANG II), and aldosterone in the plasma and urine. In contrast, 3-MA and chloroquine (CQ) suppressed the urine-concentrating capability in WD72 mice, accompanied by downregulation of AQP2 and V2R expression in the renal cortex. 3-MA and CQ further increased AQP2 and V2R expression in the renal medulla of WD72 mice. Compared with 3-MA and CQ, Rapa administration yielded completely opposite results on the above parameters in WD72 mice. In addition, 3-MA and CQ abolished the upregulation of prorenin/renin, ANG II, and aldosterone levels in the plasma and urine in WD72 mice. Taken together, our study demonstrated that autophagy regulated urine-concentrating capability through differential regulation of renal AQP2/V2R and ACE/ANG II signaling during WD.NEW & NOTEWORTHY Autophagy exhibits a double-edged effect on cell survival and plays an essential role in renal pathophysiology. We for the first time reported a novel function of autophagy that controls the urine-concentrating capability in physiological conditions. We found that water deprivation (WD) differentially regulated autophagy in the kidneys of mice in a time-dependent manner and autophagy regulates the urine-concentrating capability mainly by regulating AQP2/V2R and ACE/ANG II signaling in the renal cortex in WD mice.

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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
期刊最新文献
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